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- EMDB-29726: Cryo-EM structure of the human cardiac myosin filament -

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Basic information

Entry
Database: EMDB / ID: EMD-29726
TitleCryo-EM structure of the human cardiac myosin filament
Map data
Sample
  • Tissue: Myosin filaments isolated from human cardiac left ventricular muscle
KeywordsCardiac / Myosin / Filament / Complex / CONTRACTILE PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.01 Å
AuthorsDutta D / Nguyen V / Padron R / Craig R
Funding support United States, 4 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)AR072036 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL139883 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL164560 United States
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)AR081941 United States
CitationJournal: Nature / Year: 2023
Title: Cryo-EM structure of the human cardiac myosin filament.
Authors: Debabrata Dutta / Vu Nguyen / Kenneth S Campbell / Raúl Padrón / Roger Craig /
Abstract: Pumping of the heart is powered by filaments of the motor protein myosin that pull on actin filaments to generate cardiac contraction. In addition to myosin, the filaments contain cardiac myosin- ...Pumping of the heart is powered by filaments of the motor protein myosin that pull on actin filaments to generate cardiac contraction. In addition to myosin, the filaments contain cardiac myosin-binding protein C (cMyBP-C), which modulates contractility in response to physiological stimuli, and titin, which functions as a scaffold for filament assembly. Myosin, cMyBP-C and titin are all subject to mutation, which can lead to heart failure. Despite the central importance of cardiac myosin filaments to life, their molecular structure has remained a mystery for 60 years. Here we solve the structure of the main (cMyBP-C-containing) region of the human cardiac filament using cryo-electron microscopy. The reconstruction reveals the architecture of titin and cMyBP-C and shows how myosin's motor domains (heads) form three different types of motif (providing functional flexibility), which interact with each other and with titin and cMyBP-C to dictate filament architecture and function. The packing of myosin tails in the filament backbone is also resolved. The structure suggests how cMyBP-C helps to generate the cardiac super-relaxed state; how titin and cMyBP-C may contribute to length-dependent activation; and how mutations in myosin and cMyBP-C might disturb interactions, causing disease. The reconstruction resolves past uncertainties and integrates previous data on cardiac muscle structure and function. It provides a new paradigm for interpreting structural, physiological and clinical observations, and for the design of potential therapeutic drugs.
History
DepositionFeb 10, 2023-
Header (metadata) releaseNov 1, 2023-
Map releaseNov 1, 2023-
UpdateDec 6, 2023-
Current statusDec 6, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_29726.map.gz / Format: CCP4 / Size: 1.9 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.0873 Å
Density
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.030718578 - 2.2447846
Average (Standard dev.)0.0050151926 (±0.052523017)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions800800800
Spacing800800800
CellA=B=C: 869.83997 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: #1

Fileemd_29726_additional_1.map
Projections & Slices
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Half map: #1

Fileemd_29726_half_map_1.map
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Half map: #2

Fileemd_29726_half_map_2.map
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Sample components

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Entire : Myosin filaments isolated from human cardiac left ventricular muscle

EntireName: Myosin filaments isolated from human cardiac left ventricular muscle
Components
  • Tissue: Myosin filaments isolated from human cardiac left ventricular muscle

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Supramolecule #1: Myosin filaments isolated from human cardiac left ventricular muscle

SupramoleculeName: Myosin filaments isolated from human cardiac left ventricular muscle
type: tissue / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human) / Organ: heart

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation statefilament

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Sample preparation

BufferpH: 6.8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 61.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.2)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.2)
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 6.01 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.3.2) / Number images used: 138288
FSC plot (resolution estimation)

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